Optical Control of Lipid Rafts with Photoswitchable Ceramides

Ceramide is a pro-apoptotic sphingolipid with unique physical characteristics. Often viewed as a second messenger, its generation can modulate the structure of lipid rafts. We prepared three photoswitchable ceramides, ACe s, which contain an azobenzene photoswitch allowing for optical control over the N -acyl chain. Using combined atomic force and confocal fluorescence microscopy, we demonstrate that the ACe s enable reversible switching of lipid domains in raft-mimicking supported lipid bilayers (SLBs). In the trans -configuration, the ACe s localize into the liquid-ordered (L o ) phase. Photoisomerization to the cis -form triggers a fluidification of the L o domains, as liquid-disordered (L d ) “lakes” are formed within the rafts. Photoisomerization back to the trans -state with blue light stimulates a rigidification inside the L d phase, as the formation of small L o domains. These changes can be repeated over multiple cycles, enabling a dynamic spatiotemporal control of the lipid raft structure with light.